microRNA-328 in exosomes derived from M2 macrophages exerts a promotive effect on the progression of pulmonary fibrosis via FAM13A in a rat model.

Meng-Ying Yao, Wei-Hong Zhang, Wen-Tao Ma, Qiu-Hong Liu, Li-Hua Xing, Gao-Feng Zhao

Experimental & molecular medicine 2019 Jun 04

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Currently, exosome-enclosed microRNAs (miRs) in exhaled breath have potential for biomarker discovery in patients with pulmonary diseases. This study was performed to investigate the roles of M2 macrophage-derived exosomes expressing miR-328 in pulmonary fibrosis (PF). Microarray-based analysis was used to screen differentially expressed genes (DEGs) and regulatory miRs in PF. The miR-target relationship between FAM13A and miR-328 was confirmed. The expression of FAM13A and miR-328 was measured in PF rats, and gain- and loss-of-function assays were conducted to determine the regulatory effects of FAM13A and miR-328 on PF. In addition, exosomes derived from M2 macrophages were isolated and then cocultured with pulmonary interstitial fibroblasts to identify the role of these exosomes in PF. Furthermore, the effects of M2 macrophage-derived exosomes overexpressing miR-328 on pulmonary fibroblast proliferation and the progression of PF were assessed in vivo. miR-328 might perform a vital function in PF by regulating FAM13A. FAM13A expression was downregulated while miR-328 expression was upregulated in rats with PF, and a miR-target relationship between miR-328 and FAM13A was observed. Additionally, miR-328 overexpression and FAM13A silencing each were suggested to promote pulmonary interstitial fibroblast proliferation and the expression of Collagen 1A, Collagen 3A and α-SMA. Then, in vitro experiments demonstrated that M2 macrophage-derived exosomes overexpressing miR-328 contributed to enhanced pulmonary interstitial fibroblast proliferation and promoted PF. Furthermore, in vivo experiments confirmed the promotive effects of M2 macrophage-derived exosomes overexpressing miR-328 on the progression of PF. Collectively, the results showed that M2 macrophage-derived exosomes overexpressing miR-328 aggravate PF through the regulation of FAM13A.

Citation

Meng-Ying Yao, Wei-Hong Zhang, Wen-Tao Ma, Qiu-Hong Liu, Li-Hua Xing, Gao-Feng Zhao. microRNA-328 in exosomes derived from M2 macrophages exerts a promotive effect on the progression of pulmonary fibrosis via FAM13A in a rat model. Experimental & molecular medicine. 2019 Jun 04;51(6):1-16